A study of the plasma kinin-generating system in children with the minimal lesion, idiopathic nephrotic syndrome

• Published in: Pediatric research Vol. 9; no. 9; pp. 705 - 709
• Main Authors: Kallen, R J, Lee, S K
• Format: Journal Article
• Language: English
• Published: United States 01.09.1975
• Subjects: alpha-Macroglobulins - analysis; Aprotinin - blood; Capillary Permeability; Child; Humans; Kallikreins - blood; Kidney Glomerulus - blood supply; Kinins - biosynthesis; Nephrosis, Lipoid - blood; Nephrosis, Lipoid - etiology; Nephrotic Syndrome - blood; Nephrotic Syndrome - drug therapy; Prednisone - therapeutic use; Prekallikrein - blood; Proteinuria - drug therapy; Proteinuria - etiology; Recurrence; Remission, Spontaneous
• ISSN: 0031-3998; 1530-0447
• DOI: 10.1203/00006450-197509000-00004

Although the precise etiologic incitant of the minimal lesion idiopathic nephrotic syndrome of childhood is not known, it is likely that a host mechanism mediates the permeability alterations of the glomerular capillary wall resulting in massive proteinuria. As a first step in examining the possibility that local kinin release may account for the proteinuria in this disorder, two parameters of the plasma kinin-generating system, plasma prekallikrein and kallikrein inhibitor, were assayed during 27 nephrotic episodes in 21 corticosteroid-responsive children. Plasma kallikrein was assayed by means of its esterase activity on a synthetic arginine ester substrate, N-alpha-tosyl-L-arginine methyl ester (TAMe), after activation of Hageman factor by kaolin. This activity, after subtraction of spontaneous arginine esterase activity (i.e., TAMe esterase activity measured in plasma not exposed to kaolin) is derived from prekallikrein. Plasma prekallikrein activity in 11 normal children was 99.6 +/- 2.9 mumol TAMe hydrolyzed/ml plasma/hr (mean +/- SEM). Kallikrein inhibitor was quantified in arbitrary units. Kallifrein inhibitor activity in 11 normal children was 0.94 +/- 0.04 units. During the overt nephrotic syndrome, before initiation of intensive daily corticosteroid treatment, mean values were: prekallikrein, 58.5 +/- 7.24 mumol/ml/hr; and kallikrein inhibitor, 0.35 +/- 0.06 units. After corticosteroid-induced remission occurred, mean values were: plasma prekallikrein, 118.6 +/- 3.2 mumol/ml/hr; and kallikrein inhitor, 0.78 +/- 0.03 mumol/ml/hr. Both parameters were again assayed in 14 of the 21 children after complete cessation of corticosteroid treatment. Plasma prekallikrein was normal, 99.6 +/- 4.8 mumol/ml/hr; but kallikrein inhibitor was still somewhat depressed, 0.84 +/- 0.03 units. A subset of 9 patients had marked depression of plasma prekallikrein to levels less than 20 mumol/ml/hr and essentially undetectable inhibitor activity. Serum alpha-2 macroglobulin was elevated in nephrotic patients: mean value during relapse, 862 +/- 29 mg/100 ml; during corticosteroid-maintaining remission, 615 +/- 29 mg/100 ml. After cessation of corticosteroids, mean serum level was 481 +/- 20 mg/100 ml. The proportional reduction of plasma prekallikrein and kallikrein inhibitor suggested that an enzyme-inhibitor complex formed in vivo, perhaps at a local site of activation in proximity to the glomerular basement membrane. These data suggest that the plasma kinin-generating system may be the host effector mechanism subserving the increased glomerular capillary permeability in the minimal lesion nephrotic syndrome of childhood.